title: Relatively high risk for hepatocellular carcinoma in patients with primary biliary cirrhosis not responding to ursodeoxycholic acid.
abstract: BACKGROUND
  The reported incidence of hepatocellular carcinoma (HCC) among patients with primary biliary cirrhosis (PBC) varies from 0.7-3.8%, whereas in cirrhotic patients the risk is considerably higher. Age, male sex, cirrhosis, and portal hypertension are reported risk factors. It has been suggested that ursodeoxycholic acid (UDCA) may protect against HCC. We aimed to define risk factors for the development of HCC at the time of PBC diagnosis and to identify, among patients treated with UDCA for a long term, a subgroup that could benefit from screening.
  
  
  METHODS
  Prospective multicenter cohort study of patients with established PBC treated with 13-15 mg/kg/day UDCA. Age, sex, antimitochondrial antibodies, bilirubin, albumin, alkaline phosphatase, alanine aminotransferase, aspartate amino transferase, cirrhosis, portal hypertension, Mayo Risk Score, prognostic class (based on bilirubin and albumin levels), and response to UDCA (normalization of bilirubin and/or albumin levels) were analyzed as potential risk factors in Cox regression analysis.
  
  
  RESULTS
  Three hundred and seventy-five patients were included, median follow-up was 9.7 years. HCC occurred in nine patients, corresponding with an annual incidence of 0.2%. The factor significantly associated with the development of HCC was the response to UDCA (P<0.001). The risk for HCC was highest in the group of nonresponders to UDCA: the 10 years incidence of HCC was 9% and the 15 years incidence was 20%. The number needed to screen in this subgroup was 11.
  
  
  CONCLUSIONS
  In UDCA treated PBC patients the risk of HCC is relatively low. The main risk factor for HCC in this study was the absence of biochemical response to UDCA after 1-year treatment.
authors.affiliation: Departments of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Edith M M
authors.initials: EM
authors.lastname: Kuiper
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.forename: Rob P R
authors.initials: RP
authors.lastname: Adang
authors.forename: Carin M J
authors.initials: CM
authors.lastname: van Nieuwkerk
authors.forename: Robin
authors.initials: R
authors.lastname: Timmer
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: Piet
authors.initials: P
authors.lastname: Spoelstra
authors.forename: Hans T
authors.initials: HT
authors.lastname: Brouwer
authors.forename: Johan P H
authors.initials: JP
authors.lastname: Kuyvenhoven
authors.forename: Henk R
authors.initials: HR
authors.lastname: van Buuren
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D002423:Cause of Death; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008113:Liver Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D018579:Patient Selection; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D017211:Treatment Failure; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid